Aim:The pleiotropic effect of fibroblast growth factor 2 (FGF2) on promoting myogenesis, angiogenesis, and innervation makes it an ideal growth factor for treating volumetric muscle loss (VML) injuries. While an initial delivery of FGF2 has demonstrated enhanced regenerative potential, the sustained delivery of FGF2 from scaffolds with robust structural properties as well as biophysical and biochemical signaling cues has yet to be explored for treating VML. The goal of this study is to develop an instructive fibrin microthread scaffold with intrinsic topographic alignment cues as well as regenerative signaling cues and a physiologically relevant, sustained release of FGF2 to direct myogenesis and ultimately enhance functional muscle regeneration. Methods:Heparin was passively adsorbed or carbodiimide-conjugated to microthreads, creating a biomimetic binding strategy, mimicking FGF2 sequestration in the extracellular matrix (ECM). It was also evaluated whether FGF2 incorporated into fibrin microthreads would yield sustained release. It was hypothesized that heparin-conjugated and co-incorporated (co-inc) fibrin microthreads would facilitate sustained release of FGF2 from the scaffold and enhance in vitro myoblast proliferation and outgrowth. Results:Toluidine blue staining and Fourier transform infrared spectroscopy confirmed that carbodiimide-conjugated heparin bound to fibrin microthreads in a dose-dependent manner. Release kinetics revealed that heparin-conjugated fibrin microthreads exhibited sustained release of FGF2 over a period of one week. An in vitro assay demonstrated that FGF2 released from microthreads remained bioactive, stimulating myoblast proliferation over four days. Finally, a cellular outgrowth assay suggests that FGF2 promotes increased outgrowth onto microthreads. Conclusions:It was anticipated that the combined effects of fibrin microthread structural properties, topographic alignment cues, and FGF2 release profiles will facilitate the fabrication of a biomimetic scaffold that enhances the regeneration of functional muscle tissue for the treatment of VML injuries.

Aim: Since decades, decellularized extracellular matrix (dECM)-derived materials have received worldwide attention as promising biomaterials for tissue engineering and biomedical applications. Soluble dECM is a versatile raw material that can be easily engineered into the desired shapes and structures. However, there are still some limitations restricting its use, including low hydrophilicity and smooth surfaces, which negatively influence cell adhesion/spreading. The objective of the present study was to investigate surface modification by nitrogen/hydrogen (N₂/H₂) low-pressure cold plasma treatment as a potential technique to improve the biological response of bovine pericardium dECM films. Methods: Bovine pericardium dECM was enzymatically digested and lyophilized prior to the preparation of thin films via solvent-casting method. Changes in surface properties after plasma treatment were investigated using water contact angle (WCA) and X-ray photoelectron spectroscopy (XPS) measurements. Immunofluorescence staining and resazurin assay for human dermal fibroblasts (HDFs) cultured on the dECM films were used to assess the bioactivity of dECM films. Finally, the hemocompatibility of the films was investigated via clotting time and hemolysis assay. Results: WCA and XPS results revealed that oxygen (O)- and N-containing functional groups were incorporated onto the film surface and an increase in hydrophilicity was observed after plasma treatment. In vitro experiments showed that cell adhesion in plasma-treated dECM films is much faster if compared to the untreated controls. Moreover, the fibroblast proliferation increased after plasma surface modifications. Finally, the hemocompatibility analysis results indicated a delayed blood clotting and no hemolytic effects for all the tested samples. Conclusions: These findings confirmed the potential of dECM as raw material for biocompatible thin films fabrication. Additionally, plasma surface treatment emerged as an eco-friendly and cost-effective strategy to enhance in vitro cell attachment and proliferation on dECM films, expanding their applications in biomedicine.

Neurodegenerative diseases (NDDs) gradually affect neurons impacting both their function and structure, and they afflict millions worldwide. Detecting these conditions before symptoms arise is crucial for better prognosis and duality of life, given that the disease processes often begin years earlier. Yet, reliable and affordable methods to diagnose NDDs in these stages are currently lacking. There’s a growing interest in using circulating extracellular vesicles (EVs), like small EVs (sEVs) also known as exosomes, as potential sources of markers for screening, diagnosing, and monitoring NDDs. This interest stems from evidence showing that these EVs can carry brain pathological proteins implicated in NDD pathology, and they can even traverse the blood-brain barrier. This review focuses on the creation of EVs, particularly sEVs with a size of less than 200 nanometers, methods for isolating sEVs, and recent advancements in biosensor development to detect NDD-related markers found in sEVs. Furthermore, it explores the potential of sEVs in diagnosing four major NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and multiple system atrophy (MSA).

Nanomedicine, a convergence of nanotechnology and medical sciences, has unleashed transformative potential in healthcare. However, harnessing the benefits of nanomedicine requires a thorough understanding of its regulatory landscape. An in-depth discussion of regulatory considerations, including molecular safety assessment, harmonization of the regulatory landscape, and shaping the future of innovation, is presented in this discourse. The molecular safety assessment entails evaluating interactions between nanoparticles and biomolecules, ensuring compatibility at the molecular level. Harmonization involves developing international standards and guidelines for a consistent regulatory approach, while shaping innovations emphasizes integrating molecular safety assessments into early stages of development. Challenges encompass the need for standardized assessment methods, balancing innovation with safety, and addressing unique features of novel molecular designs. As the nanomedicine landscape evolves, effective regulatory strategies must navigate the intricate interplay of molecules and technologies, ensuring both patient access and product safety.

Aim:Polymethylmethacrylate bone cement is often used to reconstruct critical-sized defects generated by the surgical resection of spinal metastases. Residual tumor cells after a resection can drive recurrence and destabilization. Doxorubicin (DOX) is a common chemotherapeutic drug with unwanted side-effects when administered systemically. Mesoporous silica nanoparticles (NPs) are gaining attention for targeted drug delivery to bypass the negative side effects associated with systemic drug administration. An NP-functionalized cement was developed for the local release of DOX and its ability to suppress cancer cells was tested. Methods:DOX was loaded onto NPs which were then mixed into the cement. Static contact angles were measured. Drug release profiles were obtained over a period of 4 weeks. Cement constructs were incubated with two-dimensional (2D) cultures of human bone-marrow derived mesenchymal stem cells and human osteoblasts, as well as 2D and three-dimensional (3D) cultures of breast and prostate cancer cell lines. Cell metabolic activity and viability were evaluated. Cell migration and spheroid growth of cancer cell lines were assessed in collagen-coated spheroid cultures. Results:NPs were homogenously dispersed and did not alter the mechanical strength nor the wettability of the cement. A sustained DOX release profile was achieved with the addition of NPs to the bone cement. The release profile of DOX from NP cement may be modified by varying the amount of the drug loaded onto the NPs and the proportion of NPs in the cement. Cancer cells treated with the cement constructs showed a dose- and time-dependent inhibition, with minimal toxicity against healthy cells. Cancer cell migration and spheroid growth were impaired in 3D culture. Conclusions:NPs were shown to be essential for sustained DOX release from bone cement. DOX-loaded NP cement can inhibit cancer cells and impair their migration, with strong potential for in vivo translation studies.